EFFECT OF LEVOFLOXACIN, ERYTHROMYCIN OR RIFAMPICIN PRETREATMENT ON GROWTH OF LEGIONELLA-PNEUMOPHILA IN HUMAN MONOCYTES

Opsonophagocytic killing of some bacteria (Staphylococcus aureus, Pseu domonas aeruginosa) by phagocytes is enhanced by previous brief exposu re of the organism to antibiotics. We studied the regrowth of Legionel la pneumophila previously pretreated with levofloxacin, erythromycin a nd/or rifampicin in human monocytes. The MIC for the L. pneumophila is olate of levofloxacin, erythromycin and rifampicin was 0.03, 0.5 and 0 .001 mg/L, respectively. Growth of L. pneumophila from buffered charco al yeast extract (BCYE) agar for 24 h was subcultured into BYE broth c ontaining from 0 to 4x MIC of levofloxacin, erythromycin or rifampicin . After incubation at 35 degrees C in 5% CO2 for 18 h, the organisms w ere washed and opsonized with 20% heat inactivated pooled normal human serum. Thereafter, L. pneumophila was exposed to human monocytes (5:1 ratio) previously adhered to wells in tissue culture plates containin g RPMI and 10% fetal calf serum. After 0, 24, 48 and 72 h of incubatio n, quantitative cultures of lysed human monocytes were done on BCYE ag ar. Our results indicate effective inhibition on L. pneumophila at 0 h regardless of the antibiotic (levofloxacin, rifampicin or erythromyci n) or their concentrations (1x, 2x or 4x MIC). At 24, 48 and 72 h, rec overy and regrowth of L. pneumophila were both antibiotic-and concentr ation-dependent. In comparison with controls (no antibiotic pretreatme nt), peak regrowth of L. pneumophila pretreated with either 1x MIC of levofloxacin or erythromycin was delayed (48 versus 24 h) and reduced (30% of control peak regrowth). Regrowth of L. pneumophila pretreated with Ix MIC of rifampicin continued beyond 72 h. Pretreatment with lev ofloxacin at 4x MIC caused the greatest degree of growth inhibition (2 log(10)). In contrast, at 72 h, regrowth of organisms pretreated with 4x MIC of erythromycin or rifampicin was less than peak control (P < 0.01) but greater than that seen with levofloxacin (P < 0.01). The rat e and degree of regrowth of L. pneumophila pretreated with combination s of levofloxacin or erythromycin with rifampicin, or levofloxacin wit h erythromycin (all at 1x MIC) was similar to that seen with single dr ugs. Thus, significant delay and reduction of regrowth in this phagocy tic system occurred with levofloxacin only. Prolonged exposure of the organism at 4x MIC levofloxacin concentrations was effective in suppre ssing regrowth of pretreated L. pneumophila in human monocytes.